Ti-catalyzed regio- and enantioselective synthesis of unsaturated α-amino nitriles, amides, and acids.: Catalyst identification through screening of parallel libraries
Ti-catalyzed regio- and enantioselective synthesis of unsaturated α-amino nitriles, amides, and acids.: Catalyst identification through screening of parallel libraries
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DOI：
10.1021/ja994121e
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发表时间：
2000-03-22
影响因子：
15
通讯作者：
Hoveyda, AH
中科院分区：
文献类型：
--
作者：
Porter, JR;Wirschun, WG;Hoveyda, AH
由于R-氨基酸在化学和生物学中的重要性，继续寻找导致这些重要化合物以光学纯形式形成的有效方法。已经设计了几种程序，以高选择性提供R-氨基酸，但这些方案中的许多依赖于使用手性助剂。2其他方法依赖于脱氢氨基酸的催化对映选择性还原，并且已经公开了几种手性氢化催化剂，其以高产率和选择性递送光学纯的R-氨基酸。3，4最近，我们报道了一种钛催化的方法，用于芳基亚胺的不对称氰化物加成，该方法有效地提供了衍生的芳基氨基腈，并具有出色的对映体控制; 5，6通过合成和筛选平行配体库确定了最佳催化剂的身份。7随后腈的水解和胺单元的同时脱保护得到所需的光学纯的芳基R-氨基酸。在这些研究之后，我们开始研究催化不对称氰化物加成到R，β-不饱和亚胺上（方案1）。我们推断，如果这些反应进行区域选择性（1，2-对1，4-加成）和对映选择性，一个有效的途径，以各种不饱和的R-氨基酸将在手和催化不对称斯特雷克过程的一般性将是
Due to the significance of R-amino acids in chemistry and biology, the search for efficient methods that lead to the formation of these important compounds in the optically pure form continues. 1 Several procedures have been devised that afford R-amino acids in high selectivity, but many of these protocols rely on the use of chiral auxiliaries. 2 Other approaches depend on catalytic enantioselective reduction of dehydroamino acids, and several chiral hydrogenation catalysts have been disclosed that deliver optically pure R-amino acids in high yield and selectivity. 3, 4 Recently, we reported a Ti-catalyzed process for the asymmetric cyanide addition to aryl imines, which affords the derived aryl amino nitriles efficiently and with exceptional enantiocontrol; 5, 6 the identity of the optimal catalyst was determined through synthesis and screening of parallel ligand libraries. 7 Subsequent hydrolysis of the nitrile and simultaneous deprotection of the amine unit afford the desired optically pure aryl R-amino acids. These protocols thus allow access to R-amino acids that are not available by the catalytic asymmetric hydrogenation reaction.After these studies we began to examine the catalytic asymmetric cyanide addition to R, β-unsaturated imines (Scheme 1). We reasoned that if these reactions proceed regioselectively (1, 2-vs 1, 4-addition) and enantioselectively, an efficient route to various unsaturated R-amino acids would be at hand and the generality of the catalytic asymmetric Strecker process would be